Core C: Biostatistics Project Summary The scientific objective of establishing an international network for identification, evaluation, and longitudinal follow-up of families with early onset dominantly inherited Alzheimer's disease (AD) is addressed in the overview of this renewal application and in Core B: Clinical. The activities of the Core C: Biostatistics are designed to enhance the research objectives of DIAN by serving the DIAN investigators with a smooth transition from the database to statistical analyses, providing appropriate statistical analysis resources to all Cores, and developing necessary longitudinal statistical models to test the preclinical hypotheses of DIAN on all major biomarkers of AD. The major hypotheses in DIAN conjecture a period of preclinical AD in individuals who are destined to develop early onset dementia (mutation carriers) that can be detected by changes in biological fluids and in neuroimaging correlates in comparison with individuals who will not develop early onset dementia (noncarriers) and a temporal difference in preclinical changes across these correlates for mutation carriers. The methodological significance of the hypothesis is the requirement of state-of-the-art longitudinal statistical models to adequately estimate and compare the longitudinal rates of change on multi-modal disease markers during the preclinical period, and to assess their association with the risk of subsequent development of symptomatic AD.